T cells are indispensable to the immune system. At present, the basic researches have shown that the Pax5 gene deleted murine B cells can be transdifferentiated into T cells. B cells from Ebf1 and Pax5 complex heterozygous mice (Ebf1+/− Pax5+/−) can also be transdifferentiated into T cells. In addition, uncommitted multipotent progenitor cells can be obtained by converting the B progenitor cells via a retro-viral overexpressing approach, and re-differentiate into T cells. However, the generated T cells obtained by the approaches mentioned above are not perfect in functionalities, and even lead to clonal lymphoma. In conclusion, most of the key regulatory genes used by the researchers mentioned above are hematopoietic lineage master regulators, the deletion or overexpression of which would result in functional defects of the regenerated T cells or even tumors. Therefore, de novo lineage switching factors preferentially expressed in hematopoietic stem/progenitor cells, may have the potential to completely change the epigenetic paradigm, and thus achieve T cells by transdifferentiation. Only regenerated T progenitor cells obtained by complete transdifferentiation can follow the developmental process of natural physiologic T lymphocytes, differentiate and mature into functional T cells in vivo, and reduce the risk of tumorigenesis.